The purpose of this study was to investigate the effect of ultrasonic and microwave disintegration on physico-chemical and biodegradability properties of waste-activated sludge (WAS) from a municipal wastewater treatment plant. Another aim was to carry out particle size distribution (PSD) analysis as an integral component of sludge characterization to highlight the transformation mechanisms involved in pretreatment processes and better understand the biodegradation patterns of sonicated and irradiated WAS liquids examined by means of respirometric measurements. Various combinations of sonication and microwave irradiation parameters were applied to optimize operating conditions. The optimum ultrasonic density was determined as 1.5 W/mL, and energy dosages lower than 30,000 kJ/kg TS resulted in a fairly linear increase in the soluble chemical oxygen demand (SCOD) release. An irradiation time of 10 min and a temperature of 175C were selected as the optimum microwave pretreatment conditions for sludge liquefaction. The most apparent impact of ultrasonication on the PSD of COD was the shifting of the peak at the particulate fraction (> 1600 nm) toward the lowest size range (< 2 nm). Microwave heating at the selected experimental conditions and ultrasonic pretreatment at 30,000 kJ/kg TS exhibited comparable size distribution and biodegradation characteristics to those of domestic sewage.